PB1934: MEASURED OPTIMUM ANTI-SPIKE LEVEL VACCINATION STRATEGY AND ANTI-VIRAL ACCESS RESULT IN LOW COVID HOSPITALISATION AND MORTALITY IN CLL AND MBL
Authors: Yandong Shen, Jane Freeman, Ian Kerridge, Kartik Naidu, Juliette Holland, Stephen Mulligan
Journal: HemaSphere (2023)

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Patients with chronic lymphocytic leukemia (CLL) or monoclonal B-lymphocytosis (MBL) have impaired immunity. During the COVID pandemic, these patients are at high risk of severe COVID infection, hospitalisation, ICU admission and death. Mortality was very high during early pandemic waves at 30%-40%, and remains high at 10-15% during later waves. We adopted an approach of measuring anti-spike antibody response following multiple COVID-19 vaccine doses to assess the optimum individual response. Compared to post-2 vaccine doses (Shen, BJH, 2022), we demonstrated significantly increased seroconversion and anti-spike antibody levels in patients with CLL or MBL after multiple sequential doses (Shen, Blood, 2022). Australia lifted most COVID restrictions in early December 2021, then all in April 2022. From December 2021, there was a dramatic increase COVID infections from ~200 to >40,000 cases per day. Tixagevimab plus cilgavimab (Evusheld®) was not available until August 2022. Aims: We aimed to evaluate outcomes from COVID infection in CLL and MBL of infection, hospitalisation, ICU admission, and mortality rates, and anti-nucleocapsid (NC) levels. Methods: PCR or RAT confirmed COVID infection were assessed during clinical follow-up and by questionnaire. Levels of anti-SARS-CoV-2 antibody were measured using the Abbott Diagnostics quantitative anti-spike, and qualitative NC assays. The latest anti-spike antibody level prior to infection was used for analysis. Results: With data from 123 patients (102 CLL and 21 MBL), 55 CLL (53.9%) and 12 MBL (57.1%) had PCR or RAT confirmed COVID-19 infection; and 4 had a second infection. Most (53/67 79.1%) recovered in 3-14 days. In total, there were 4 (7.3%) CLL patients hospitalized with duration of 3 to 8 weeks. There was 1 death in a CLL patient (1/55 = 1.8%) due to acute anuric renal failure 4 weeks after COVID diagnosis. No MBL patient was hospitalised or died. Of the total 67 CLL and MBL infected patients, 21 did not receive any medication and 20 had symptom-relief (paracetamol). There were 35 (52.2%) who received antiviral therapy; Lagevrio® (molnupiravir) (15), Paxlovid® (nirmatrelvir + ritonavir) (15) or Remdesivir (5). Only 6 of 67 had received Evusheld® prior to COVID infection. There were 89 patients with positive anti-spike levels (91.8%, 89/98 where data was available, excluding levels measured post Evusheld). The anti-spike levels in infected patients prior to infection (6036.5 AU/mL, 60 positive, 7 negative) was significantly lower compared to those never infected (14319.1 AU/mL, 50 positive, 0 negative) (p=0.038). Anti-NC antibody was detected in 15 of 43 infected patients (34.9%) within 2 months of infection. Of 11 patients followed for more than 6 months, 6 of 11 (54.5%) lost detectable NC positivity. Summary/Conclusion: The overall hospitalization rate of 7.3% and mortality rate of 1.5% in our COVID-infected CLL and clinical MBL cohort were significantly lower than those reported in early waves, and lower than rates reported in North America and Europe in late 2022. This suggests that a multiple dose vaccination strategy targeted to achieve a measured, optimum, anti-spike antibody level, with associated neutralising antibody and T-cell responses, is the key factor, as well as relatively easy access to anti-viral therapy. Prophylactic antibodies in 6/67 patients may have contributed in this small group. CLL patients have an impaired seroconversion of anti-NC antibodies at 34.9%, and half lose anti-NC antibodies by 6 months.Keywords: COVID-19, B-CLL, Vaccination, Chronic lymphocytic leukemia